Diseases, dystrophies disorders

Human creatine kinase -MM MAK33 IgGl Cardiac disease, mitochondrial disorders, inflammatory myopathies, myasthenia, polymyositis, McArdle s disease, NMJ disorders, muscular dystrophy, ALS, hypo and hyperthyroid disorders, central core disease, acid maltase deficiency, myoglobinuria, rhabdomyolysis, motor neuron diseases, A. thaliana A. thaliana 2S2 seed storage protein SP + 0.02-0.4% TSP of fresh leaf extract (10-12% TSP of intercellular fluid) 52... 

Inositols, ie, hexaliydrobenzenehexols, are sugars that have received increasing study and are useful in the treatment of a wide variety of human disorders, including vascular disease, cancer, cirrhosis of the Hver, frostbite, and muscular dystrophy (269). Myoinositol esters prepared by reaction with lower fatty acid anhydrides are useful as Hver medicines and nonionic surfactants the aluminum and ammonium salts of inositol hexasulfate are useful anticancer agents (270). Tetraarjloxybenzoquinones are intermediates in the preparation of dioxazine dyes (266,271). The synthesis of hexakis(aryloxy)benzenes has also beenpubUshed (272). 

Scriver CR et al (editors) The Metabolic and Molecular Bases of Inherited Disease, 8th ed. McGraw-Hill, 2001. (This comprehensive four-volume text contains coverage of malignant hyperthermia [Chapter 9], channelopathies [Chapter 204], hypertrophic cardiomyopathy [Chapter 213]> the muscular dystrophies [Chapter 216], and disorders of intermediate filaments and their associated proteins [Chapter 221].)... 

Other leukodystrophies are associated with the lysosomal and peroxisomal disorders in which specific lipids or other substances accumulate due to a deficiency in a catabolic enzyme - for example Krabbe s disease, meta-chromatic leukodystrophy (MLD) and adrenoleuko-dystrophy (ALD) [1,2]. (These are discussed in detail in Ch. 40.) Similarly, disorders of amino acid metabolism can lead to hypomyelination - for example phenylketonuria and Canavan s disease (spongy degeneration) [1, 2, 25] (Ch. 40). The composition of myelin in the genetically... 

Duchenne and Becker muscular dystrophies (DMD and BMD) are X-linked, allelic, neuromuscular diseases. DMD/BMD are characterized by progressive muscular weakness and degeneration of skeletal muscle. DMD is the most common recessive lethal disease, with an incidence of approximately 1 in 3500 newborns, and according to estimates, one-third of the cases are linked with new mutations (M3). Clinical symptoms of the disease appear earlier, by 2 to 3 years of age, in the form of retarded motor development. Progressive symptomatic children show weakness and wasting of muscle and are usually wheelchair bound approximately by the age of 11-12 years. It has been reported that most patients die at about the age of 20 due to pneumonia, which is related to chronic respiratory insufficiency. BMD—being the rarer allelic disorder—has a milder clinical course with slower disease progression. The BMD-affected patients usually survive beyond the age of 30. 

The signs and symptoms of some genetic conditions tend to become more severe and appear at an earlier age as the disorder is passed from one generation to the next. This phenomenon is called anticipation. Anticipation is most often seen with certain genetic disorders of the nervous system, such as Huntington disease, myotonic dystrophy, and fragile X syndrome. 

Williams RJ. The genetotrophic approach to metabolic disease. In Exploratory Concepts in Muscular Dystrophy and Related Disorders. Amsterdam, The Netherlands Excerpta Medica Foundation, 1967, 10311. 

Aging (skin and other tissues), myocardial infarct or stroke, inflammation, rheumatoid arthritis, atherosclerosis, pulmonary disorders (asthma and chronic obstructive pulmonary diseases), radiation injury, organ transplant rejection, psoriasis, hypertension, AIDS, multiple types of cancer, neuro-degenerative diseases (Parkinson s), diabetes, muscular dystrophy... 

Diseases of muscle are usually classified as muscular dystrophies, inflammatory or congenital myopathies, metabolic disorders affecting the muscle, and neurological diseases affecting the innervation of the muscle (so-called motor neuron diseases). In the past, the energy metabolism of some muscular diseases... 

Pain, muscular weakness, cramps and ease of fatigue are the most usual symptoms of muscular disease. In most cases, it is diseases of the vascular or nervous system or problems with the processes providing energy within the muscle that are responsible for clinical problems with muscles. Other clinical problems include the muscular dystrophies, myotonic disorders, inflammatory myopathies and disorders of neuromuscular transmission (see Walton, 1996). The best known is Duchenne muscular dystrophy. 

Myotonic dystrophy is a generalized adult-onset disorder with muscular spasms, weakness, and many other symptoms.11 It is one of the triple-repeat diseases (Table 26-4). The affected gene encodes a protein kinase of unknown function. The corresponding mRNA transcript has -2400 nucleotides. The gene has a CTG repeat (CTG) near the 3 -end with n< 30 normally. For persons with the mildest cases of myotonic dystrophy n may be over 50 while in severe cases it may be as high as 2000. As in other triple-repeat diseases the repeat number tends to increase in successive generations of people as does the severity of the diseased... 

Whereas many metabolic defects affect only a small number of individuals, emotional illnesses including depression, schizophrenia, and other affective disorders at one time or another afflict a large fraction of the population. Autism affects thousands of children.1055 Parkinson disease and Alzheimer disease are just two of a number of degenerative neural diseases attacking older people. Less commonly, young persons contact multiple sclerosis and muscular dystrophy, which is often a disease of neuromuscular junctions. 

Cysteine proteases play key roles in the pathogenesis of a variety of disease states including osteoporosis [49], muscular dystrophy [50] and several CNS-related disorders [51]. A 100-member library of a-ketoamides 50 was generated via a two-step one-pot synthesis, in which the initial condensation was followed by a pyridinium dichromate (PDC) oxidation (Scheme 11.9). Yields were respectable, ranging from 53 to 75%. Note that a-ketoamides are potential reversible inhibitors with the ability to form hemi-thioacetals with the active thiol of cysteine residues. 

Biochemically, I-cell disease is characterized by excessive secretion of newly synthesized lysosomal enzymes into body fluids and concomitant loss of respective intracellular activities in fibroblasts. Shown in Table 17-1 are representative lysosomal enzyme activity levels in serum from patients with I-cell disease and those with the closely related disorder pseudo-Hurler poly dystrophy, indicating significantly increased levels of lysosomal enzyme activity. Germane to the biochemical diagnosis is the characteristic pattern of lysosomal enzyme deficiency in cultured fibroblasts, that is, an increase in the ratio of extracellular to intracellular enzyme activity (Table 17-2). It is interesting to note that not all lysosomal (i.e. intracellular)... 

In contrast to arsenic, trace concentrations of selenium are essential for human and animal health. Until the late 1980s, the only known metabolic role for selenium in mammals was as a component of the enzyme glutathione peroxidase (GSH-Px), an anti-oxidant that prevents cell degeneration. There is now growing evidence, however, that a seleno-enzyme is involved in the synthesis of thyroid hormones (Arthur and Beckett, 1989 G. F. Combs and S. B. Combs, 1986). Selenium dehciency has been linked to cancer, AIDS, heart disease, muscular dystrophy, multiple sclerosis, osteoarthropathy, immune system and reproductive disorders in humans, and white muscle disease in animals (Levander,... 

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